# Impact of the intestinal microbiota on CAR T cell therapy response

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $46,036

## Abstract

Abstract:
According to the National Cancer Institute, every 9 minutes a person in the USA dies from a
blood cancer1. While initial responses are achievable with conventional chemotherapy,
relapsed/refractory disease remains a significant problem. Chimeric antigen receptor (CAR) T
cell-based immunotherapy is a revolutionarily new approach against these stubborn cancers.
Although several clinical trials have shown remarkable efficacy, there remains a subset of
patients who do not respond to CAR T therapy and/or experience toxicity as a result of immune
activation in the form of cytokine release syndrome or immune effector cell-associated
neurotoxicity syndrome (ICANS)2-6. As
preserving
of
this
a result, managing these iatrogenic toxicities while still
high on-target efficacy has become a fundamental part of the ongoing development
immunotherapy. To date, several studies have demonstrated the strong interplay
between commensal microbiota and its effect on both the innate and adaptive immune system,
such as the regulation of T cell function7-18. Studies suggest that the intestinal microbiota may
be a crucial host factor that modulates the response to immunotherapy7,8,19-21. Lymphodepleting
conditioning and administration of antibiotics regularly disrupt the natural intestinal flora leading
to dysbiosis and expansion of unfavorable antibiotic-resistance pathogenic taxa22. Although the
microbiome has been associated with clinical response in allogeneic-hematopoietic stem cell
transplants, checkpoint blockade, and adoptive T cell therapy10,20,23-26, it is still unknown as to
how microbiome manipulations affect CAR T cell therapy response. Preliminary data from our
center shows that exposure to antibiotics prior to CAR T cell infusion decreases overall survival
and progression free survival of patients. Additionally, we have found that specific bacterial taxa
in the baseline stool of patients prior to CAR T cell infusion, are associated with complete
response. These
enhanced
preliminary studies support
outcome of CAR T cell therapy.
a
causal
role
for
the
intestinal
microbiota
in
The central hypothesis for this project is that strategic
microbiota modulation can enhance CAR T cell therapy response by preserving favorable taxa
for improved effector function of CAR T cells via a pro-inflammatory milieu. This hypothesis will
be tested by pursuing two project aims: 1) Investigating the role of the intestinal microbiota on
CAR T Cell therapy response; and 2) Evaluating the impact of broad-spectrum antibiotics on
CAR T cell effector function.

## Key facts

- **NIH application ID:** 10236126
- **Project number:** 1F31CA261086-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Pamela Herrera
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236126

## Citation

> US National Institutes of Health, RePORTER application 10236126, Impact of the intestinal microbiota on CAR T cell therapy response (1F31CA261086-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10236126. Licensed CC0.

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